The family Paramyxoviridae are negative strand RNA viruses known to be responsible for a variety of human and veterinary diseases. The family contains four genera: (i) Paramyxovirus (Sendai virus; parainfluenza virus, types I and III; mumps virus), (ii) Morbillivirus (measles virus; rinderpest virus; phocine distemper virus; and canine distemper virus, (iii) Rubulavirus (Simian virus type V; Newcastle disease virus), and (iv) Pneumovirus (human respiratory syncytial virus; bovine respiratory syncytial virus).
Paramyxoviridae viruses are enveloped, so possess membrane ‘spike’ glycoproteins which are responsible for viral attachment to cell surfaces via a specific receptor and for mediating virus-cell membrane fusion. Subsequent to receptor binding, these viruses enter cells by direct fusion of the viral and host cell membranes. Viruses which fuse at the target cell membrane in a pH-independent manner are activated for fusion by the receptor binding event itself triggering conformational changes in the envelope glycoprotein. The ability of viruses to fuse directly with the target cell membrane is strongly associated with a tendency to trigger membrane fusion between infected and neighboring uninfected cells, the visible outcome of which is the formation of large multinucleated syncytia centering on a single infected cell.
Unmodified mumps virus administered as a tissue culture supernatant to 90 patients with terminal malignancies by intratumoral, oral, rectal or intravenous inoculation, or by inhalation, and resulted in significant tumor regressions (between 50 and 100%) in 37 of the patients treated, with minor responses in a further 42 patients (Asada 1974 Cancer 34 1907). The activity of mumps virus was not confined to a single tumor type, but was apparent in a range of different epithelial and nonepithelial malignancies.
Newcastle disease virus, an avian Paramyxovirus, has been used to infect cancer cells which have been removed from the patient, and are then irradiated and administered to the patient as a vaccine to elicit an antitumor immune response.
While certain Paramyxoviridae viruses have been used for cancer treatment, there is a need in the art for Paramyxoviridae viruses which are selectively cytotoxic for tumor cells such that the virus will spread rapidly and selectively through neoplastic tissues while sparing normal host tissues. There also is a need for a convenient and reliable method for monitoring the spread of the virus and the virus load in the treated patient.